Microblister Skin Grafting

ABSTRACT

The present invention generally relates to devices for harvesting a skin graft(s). The present invention provides a blister raising device integrated with a member for cutting the blister.

REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of, and priority to, as acontinuation of U.S. patent application Ser. No. 13/839,518, filed onMar. 15, 2013, which claims the benefit of, and priority to, as acontinuation-in-part of U.S. patent application Ser. No. 13/346,329filed Jan. 9, 2012, which claims the benefit of, and priority to, ofU.S. Provisional Application No. 61/567,946, filed Dec. 7, 2011. U.S.patent application Ser. No. 13/839,518 also claims the benefit of, andpriority to, as a continuation-in-part of U.S. patent application Ser.No. 13/346,318 filed Jan. 9, 2012, which is a continuation-in-part ofU.S. patent application Ser. No. 12/851,656 filed Aug. 6, 2010. U.S.patent application Ser. No. 13/839,518 also claims the benefit of, andpriority to, as a continuation-in-part of U.S. patent application Ser.No. 12/851,621 filed Aug. 6, 2010; U.S. patent application Ser. No.12/851,703 filed Aug. 6, 2010; and U.S. patent application Ser. No.12/851,682 filed Aug. 6, 2010. The contents of each of theabove-referenced related applications are herein incorporated byreference in its entirety.

FIELD OF THE INVENTION

The present invention generally relates to devices and methods forgenerating and transferring skin grafts.

BACKGROUND

Skin is the largest organ of the human body, representing approximately16% of a person's total body weight. Because it interfaces with theenvironment, skin has an important function in body defense, acting asan anatomical barrier from pathogens and other environmental substances.Skin also provides a semi-permeable barrier that prevents excessivefluid loss while ensuring that essential nutrients are not washed out ofthe body. Other functions of skin include insulation, temperatureregulation, and sensation. Skin tissue may be subject to many forms ofdamage, including burns, trauma, disease, and depigmentation (e.g.,vitiligo).

Skin grafts are often used to repair such skin damage. Skin grafting isa surgical procedure in which a section of skin is removed from one areaof a person's body (autograft), removed from another human source(allograft), or removed from another animal (xenograft), andtransplanted to a recipient site of a patient, such as a wound site.

As with any surgical procedure, skin grafting involves certain risks.Complications may include graft failure, rejection of the skin graft,infections at donor or recipient site, or autograft donor sites oozingfluid and blood as they heal. Certain of these complications (e.g.,graft failure and rejection of the skin graft) may be mitigated by usingan autograft instead of an allograft or a xenograft.

A problem encountered when using an autograft is that skin is taken fromanother area of a person's body to produce the graft, resulting intrauma and wound generation at the donor site. Generally, the size ofthe graft matches the size of the recipient site, and thus a largerecipient site requires removal of a large section of skin from a donorsite, leading to increased pain and discomfort and longer healing time.Additionally, as the size of the section of skin removed from the donorsite increases, so does the possibility of infection.

Moreover, skin grafts are often difficult to obtain due to the tendencyof the skin layer being cut to curl or fold over onto itself or thesurgical instrument (e.g., dermatome), thereby comprising the integrityof the graft and making it unsuitable for use. This folding/curlingtendency is particularly problematic the thinner the layer is that isbeing obtained, such as the epidermal layer.

While techniques have been developed for obtaining smaller micrograftsthat can be transferred onto a substrate for expansion prior totransplantation, such micrografts tend to clump together or can flip orfold during cutting, thereby comprising the integrity of the micrograftsuch that it will not properly grow on the substrate. As such, multiplecutting attempts are often necessary before a suitable, planar graft ormicrograft is obtained, thereby producing multiple wound sites, leadingto extreme discomfort, longer healing time, and a greater risk ofinfection.

Harvesting of a skin graft may be accomplished by many differenttechniques, and the technique used will depend on the type of graft tobe harvested. A common technique to harvest a skin graft includessuction blistering. Suction blistering typically involves a heat sourceto warm the skin which facilitates blister formation.

The heat source of a suction blistering device can become overheated andburn out, causing inconsistent blister formation and potential harm tothe patient. Thus, there is a need for a skin graft harvesting devicewith design features that prevent the device from overheating.

Current skin graft harvesting devices do not include means to monitorthe development of suction blisters formation. Without such means, thedevice may be applied for overly long periods of time causing excessivediscomfort or harm to the patient, or insufficient periods of time forcausing blister formation. Thus, there is a need for a skin graftharvesting device with design features that allow the user to visuallymonitor the development of suction blisters on a patient.

A common technique for harvesting a skin graft includes creating one ormore suction blisters, cutting the blister, and transferring the blisterto a substrate, for example Tegaderm®. If the substrate is notsufficiently contacted with the suction blister, the blister won'ttransfer and will thus be unusable. As such, there is a need for a skingrafting device with design features that ensure full contact betweenthe substrate and suction blister.

SUMMARY

The present invention provides devices for generating and harvesting askin graft having improved design features for ensuring sufficient andconsistent blister formation and reducing patient harm and discomfort.

In one aspect, the invention provides a device for generating andharvesting a skin graft having design features that prevent a heatingelement in the device from overheating and burning out. The deviceincludes a head that contains a heating element for raising at least oneblister, a hollow body configured for placement on a skin surface, atleast one plate member and a cutting member, both integrated within thehollow body. Preferably, the heating element radiates heat between atemperature of about 100° C. to about 750° C. In a particularembodiment, the heating element radiates heat at a temperature of about500° C. In certain aspects, the heating element radiates wavelenthsranging from about 10 nanometers to about 3000 nanometers, or anyspecific value within said range. Suitable materials for the heatingelement include, for example, nichrome wire.

The cutting member can be a second plate member integrated within thehollow body that is movable with respect to the other plate member(s) tocut the raised blister.

The plate member includes a surface that is configured for attenuatingthe reflection of heat emitted from the heating element. The surfaceconfigured for attenuating heat reflection includes a material thatsubstantially absorbs the electromagnetic radiation emitted from theheating element contained within the head of the device. Suitablematerials include, for example, thermoplastic polymers, includingflouropolymers such as polytetrafluoroethylene. Preferably, the materialis a dark colored material, such as a black, brown, purple or bluecolored material. Alternatively, the surface that attenuates heatreflection can be electroplated, anodized, painted (e.g., a dark colorsuch as black, brown, purple or blue) or abraded.

In a second aspect, the invention provides a device for generating andharvesting a skin graft having design features that allow a user, suchas a clinician, to visually monitor blister formation. The deviceincludes a head that contains a heating mechanism for raising at leastone blister and at least one viewing window integrated within the headfor monitoring blister formation. The device further includes a hollowbody configured for placement on a skin surface, at least one platemember and a cutting member, both integrated within the hollow body. Thecutting member can be a second plate member integrated within the hollowbody that is movable with respect to the other plate member(s) to cutthe raised blister.

The viewing window is preferably made of a substantially transparentmaterial, such as an optical polymer, glass or crystal. Such materialsmay include an anti-fog treatment, anti-scratch coating, or anti-glarecoating. In certain aspects, at least a portion of the viewing windowincludes a magnification lens. In another aspect, the viewing window caninclude at least one calibration mark for monitoring blister formation.The viewing window may simultaneously serve as an optical shield andattenuate the entrance of ambient light.

In a third aspect, the invention provides a device for generating andharvesting a skin graft having design features for monitoring blisterformation that include a gauge integrated within the body of the device.The device includes a head comprising a mechanism for raising one ormore blisters, a hollow body configured for placement on skin, a platemember and a cutting member integrated within the hollow body. Thecutting member can be a second plate member integrated within the hollowbody that is movable with respect to the other plate member(s) to cutthe raised blister.

The plate member includes one or more holes through which the one ormore blisters are raised, and a gauge integrated within the plate formonitoring blister formation within the one or more holes. The holeshave a depth substantially equal to the thickness of the plate member.The gauge is proximal to one or more of the holes through which theblisters are raised. In certain aspects, the gauge is a counter-borewithin one or more of the holes in the plate member. The counter borecan be about one-half to three-quarters of the depth of the hole.Alternatively, the gauge is a calibration mark proximal to one or moreof the holes in the plate member. For example, the calibration mark canbe laser etched or painted onto the plate next to one or more holes, oron the inner wall of one or more holes within the plate.

In a fourth aspect, the invention provides a device for generating andharvesting a skin graft having design features for improving heattransfer to facilitate blister formation. Such devices include a headthat contains a heating mechanism for raising at least one blister, anda transparent or translucent surface distal to the heating mechanism fortransferring heat from the heating mechanism to the body of the device.The device further includes further includes a hollow body configuredfor placement on a skin surface, at least one plate member and a cuttingmember, both integrated within the hollow body. The cutting member canbe a second plate member integrated within the hollow body that ismovable with respect to the other plate member(s) to cut the raisedblister.

The transparent or translucent surface is preferably made of a materialthat allows light having a wavelength between about 10 nanometers toabout 3000 nanometers to be transmitted therethrough (e.g., about 180 nmto about 2500 nm). Suitable materials include, for example, crystallinematerials such as, sapphire, quartz, silicon, garnet, sillenite, fusedquartz, titanium dioxide, zinc selenide, calcium fluoride, bariumfluoride, zinc sulphide, caesium iodide, germanium, thalliumbromo-iodide, lithium fluoride, magnesium fluoride, potassium bromide,sodium chloride, or strontium fluoride; or glass materials such assilica glass, fused silica, fluoride glass, aluminosilicate glass,phosphate glass, borate glass, chalcogenide glass, or a polymer glass.

In certain aspects, the head of the device includes two transparent ortranslucent surfaces distal to the heating mechanism, configured suchthat the two surfaces contain an airspace inbetween. The two surfacescan be made of the same material, or different materials. In aparticular embodiment, the two surfaces are both a glass material.

In a fifth aspect, the invention provides a device for generating andharvesting a skin graft having design features for ensuring the captureand transfer of blisters onto a substrate. Such devices include amechanism for raising at least one blister, a hollow body configured forplacement on skin, at least one plate member integrated within the bodyand including at least one hole through which the blister is raised, asubstrate removably coupled to the plate member, and a substratecompression mechanism movably coupled to the body. The substratecompression mechanism includes an actuator member coupled to acompression member. Actuation of the compression mechanism removablycouples the compression member onto the substrate to ensure full contactbetween the substrate and the raised blister.

The device further includes a cutter member integrated within the bodyfor cutting the blister. The cutting member can be a second plate memberintegrated within the hollow body that is movable with respect to theother plate member(s) to cut the raised blister. The device isconfigured such that the blister is attached to the substrate uponcutting the blister.

The compression member is movably coupled to the hollow body via anaxle, a hinge, or similar mechanism that allows the compression memberto be removably applied to the substrate. The actuation member can be ahandle coupled to the compression member to facilitate application ofthe compression member to the substrate.

The compression member can be substantially the same size and shape asthe substrate. For example, the compression member can be substantiallysquare or rectangular in shape having the same dimensions as thesubstrate. Alternatively, the compression member can be cylindrical inshape and configured to roll along the surface of the substrate whenactuated. For example, a cylindrical compression member can beconfigured to rotate about the longitudinal axis of a movable arm,whereby actuation of the arm in a horizontal direction translates intorotation of the compression member about the arm to roll the cylindricalmember across the substrate

The compression member can be made of any substantially solid material,such as any elemental metal, metal alloy, glass, crystal or polymer. Thecompression member is preferably reusable. However, in certain aspects,the compression member can be disposable.

The present invention also provides devices for producing skin graftmaterial and methods for manufacturing components for use in devices forproducing skin graft material. The invention provides manufacturingmethods for creating plates, preferably metallic plates, for use inpreparing skin grafts. Manufacturing methods as described herein areuseful to fabricate plates for use in devices as described below.

Methods of the invention result in plates for use in harvesting skingrafts produced by the application of blistering to a donor site.Methods of the invention involve the generation of a plurality of plateshaving substantially planar mating surfaces from a material, preferablya metallic material. Preferably, at least one of the plates hassubstantially uniform thickness throughout the plate. In certainembodiments, each of the plurality of plates has a substantially uniformthickness throughout each plate and/or with respect to each other. Theplurality of plates can be generated from the same material, ordifferent materials.

A plurality of coupling members for coupling the plurality of platestogether in a stacked configuration are preferably generated from thesame material as at least one or more of the plate members such that thecoupling members are substantially uniform in thickness with respect toeach other and the at least one plate member, and contain substantiallythe same planar surface with respect to each other and the at least oneof the plate member.

According to one aspect of the invention, a plurality plates aremanufactured from the same sheet stock of material. For example, asingle sheet stock of material is divided into a plurality of sectionshaving uniform shape and size with respect to each other, each sectioncorresponding to an individual plate member. At least one opening (e.g.hole or slot) is formed in each of the plate members such that theopenings are in concentric alignment when the plate members areassembled in a stacked configuration.

In certain embodiments, the plurality of coupling members for couplingthe plate members together in a stacked configuration are also formedfrom the same sheet stock from which the plate members are generated.Fabrication of the coupling members does not substantially change theplanar surface of the plates, such that the plates are stackable in aform-fitting manner and subsequently movable with respect to oneanother. The coupling members are disposed between the plate members.The coupling members can be disposed along the outer surface of theplate members, or between one or more openings (e.g., holes or slots)formed within each plate. In certain aspects, the coupling members forma frangible section between the plates that is broken upon movement ofthe plates with respect to each other in operation, as described below.Optionally, a portion of the plate material at or around the site of thecoupling is removed to accommodate at least a portion of the couplingmember and forming a depression at or around the frangible section.

Preferred methods for fabricating plates for use in skin graft generatordevices involve obtaining one or more plates of substantially uniformthickness and forming holes in the plates that align upon stacking.Plates preferably have integrated coupling members that do notsubstantially alter the thickness of the plates and allow for couplingof the plates via a frangible linkage. In operation, the plates aremoved in order to break the coupling and to cut a graft from a skinblister formed by the device into which the plates are placed.Preferably, there are three plates, with a central plate having openings(e.g., holes or slots) that form a cutting surface. In operation, theplates are moved such that the cutting surface interacts with blistersprotruding through aligned openings in a plate below. Ideally, couplingmembers are substantially uniform in shape and size and the frangiblelinkage is laser welded, but may also be a mechanical stamp, amechanical punch, a weld, epoxy or other adhesive, formed via mechanicalcompression, snap fit, tongue and groove, post and bar, frangible pin orother known connectors.

Plates manufactured as described herein are useful in a device forreliably generating skin micrografts in a single attempt. A device ofthe invention is configured to generate a plurality of substantiallyplanar micrografts in a single cutting motion. Devices of the inventionare further capable of simultaneously transferring generated micrograftsonto a substrate. Devices of the invention are particularly well-suitedfor generating and transferring a plurality of substantially planarepidermal micrografts.

In certain aspects, the invention provides a device that includes a bodyhaving a bottom surface configured for placement on skin, a mechanismfor raising at least one blister on the skin, and a cutter configured tocut formed blisters in order to produce grafts for transplantation.

The cutter may include a plurality of plates, each plate having an arrayof openings (e.g., an array of holes or slots). In certain embodimentsthe openings are substantially cylindrical in shape. The openings in thearrays are of a size to facilitate production of a plurality of graftsfrom formed blisters. The openings can range in size from about 1 mm toabout 12 mm diameter. In a particular embodiment, the openings are nogreater than about 2 mm in diameter.

At least one of the plates is movable relative to the other plates. Theplurality of plates in the cutter are configured such that asubstantially planar graft (i.e., one that is not curled, folded orclumped) is produced.

The mechanism for raising the at least one skin blister can be a vacuumsource, a heat source (e.g., a light source or warm air), or acombination of both.

Once the blister(s) is generated, a removable substrate is applied tothe blister simultaneously transfer/retain the blister upon cutting. Thesubstrate can include an adhesive to facilitate attachment of theblister to the substrate.

The device of the invention may further include a strap for securelycoupling the device against a skin surface such as the inner thigh orbuttocks. The strap may be adjustable in size, or may be a fixed size.In certain embodiments, the strap is a belt/loop fastener. In otherembodiments, the strap is a metal or plastic cuff configured to forattachment around the upper thigh.

In another aspect, the invention provides a device for obtaining a skingraft that includes a hollow body having a bottom surface configured forplacement on skin, a mechanism for raising at least one blister, and aplurality of plates, each plate including an array of holes configuredso as to maintain the integrity of a graft produced by cutting theraised blister.

In certain embodiments the openings in the hole array of each plate aresubstantially cylindrical in shape and are of a size to facilitateproduction of a substantially planar graft. For example, the holes canrange in size from 1 mm to a 12 mm diameter, or any specific value inbetween such range. In a particular embodiment, the openings in the holearrays are no greater than about 2 mm in diameter.

The mechanism for raising the at least one skin blister can be a vacuumsource, a heat source (e.g., a light source or warm air), or acombination of both.

A substrate removably connected to the body of the device directlycontacts the generated blister(s) such that upon cutting of the blister,the cut portion of skin is attached to the substrate. The substrate caninclude an adhesive to facilitate attachment of the blister to thesubstrate.

The device may further include a strap for securely coupling the deviceagainst a skin surface such as the inner thigh or buttocks. The strapmay be adjustable in size, or may be a fixed size. In certainembodiments, the strap is a belt/loop fastener. In other embodiments,the strap is a metal or plastic cuff configured to for attachment aroundthe upper thigh.

In yet another aspect, the invention provides a cutting device thatincludes a first plate having at least one opening, a second platehaving at least one opening, the second plate being attached to saidfirst plate, and a third plate having at least one opening, the thirdplate being attached to said second plate. At least one of the plates ismovable with respect to the other plates. For example, the second platemay be movable with respect to the first and/or third plates. In otherembodiments, the third plate may be stationary in operation with respectto at least one of said first and second plates. In certain embodiments,the second plate is attached to said first plate via at least onefrangible section. The frangible section is broken upon movement of saidplates with respect to each other. The frangible coupling of the platemembers to each other can be accomplished using a mechanical stampingtechnique, a mechanical punch technique, spot welding, an epoxy, anadhesive, mechanical compression, a snap-fit assembly, a tongue andgroove assembly, a post and bar assembly, a frangible pin, or anycombination thereof.

At least one of the openings in the first, second or third plate definesa cutting surface. In certain embodiments, the cutting surface on one ofthe plates engages a cutting surface on at least one other of saidplates in operation (i.e., when at least one of the plates is moved withrespect to the other plates). In certain embodiments, the opening in atleast one of the plates moves with respect to the openings in at leastanother of said plates, thereby to perform a cutting action.

In certain embodiments, the first, second and third plates each includea plurality of openings that are concentrically aligned with respect toeach other in a home position, and offset with respect to each other inan operating position (i.e., when at least one of the plates movesrespect to the other plates).

In yet another aspect of the invention, two part systems for harvestingof skin microblisters are disclosed. The two parts are a harvester thatis adapted for attachment to a target region of skin and head whichdelivers negative pressure and/or heat to at least portions of the skinengages by the harvester.

More specifically, the head is adapted for coupling to a cutting body(‘harvester”) that is disposable on a patient's skin and further adaptedfor coupling to a vacuum source, the head further providing a sealingsurface to engage with a mating surface on the cutting body such that,when the head is engaged with the cutting body on a patient's skin, aevacuated chamber is formed over a target region of skin; and,preferably, a heating element for raising the temperature of the targetregion of skin and, further preferably at least one viewing window forobserving blisters formed by heating the skin in the evacuated chamber.

In certain embodiments the window is formed on at least one side surfaceof the head at a non-parallel angle to the patient skin so skin blistersbeing raised in the chamber can be more readily observed. The head canfurther include at least one light source, such as a light emittingdiode (LED) for illuminating skin blisters as they are being raised.

The viewing window is preferably composed of a substantially transparentmaterial, such as an optical polymer, an optical glass, and an opticalcrystal and at least a portion of the viewing window further comprises amagnification lens, e.g., that magnifies objects at a magnificationranging from about 2× to about 100×. The viewing window can also includeone or more materials selected from an anti-fogging material, ananti-scratch coating, and an anti-glare coating and, preferably, isformed of a heat resistant material. The viewing window comprises anocular shield configured for attenuating entrance of ambient light.

The head can further include a heating element that is a resistiveelectrical heating element. The head can also include at least onetemperature measuring element, such as a thermistor, for measuring thetemperature of the skin or evacuated chamber.

The harvester is configured for placement on a target region of apatient's skin and further adapted to form a sealing engagement with ahead that provides negative pressure to the target region such that thetarget region of skin is embraced within an evacuated chamber

In one embodiment, the harvester further includes at least one alignmentplate having a plurality of holes through which skin blisters can beraised in the presence of negative pressure; and a cutting plate havingat least one cutting surface for cleaving skin blisters after they areformed within the chamber.

At least a part of the harvester e.g., a top alignment plate, can beformed of a radiation absorbing material, such as a fluoropolymersurface coating or layer to enhance heating of the skin.

In another preferred embodiment, the harvestor includes a top alignmentplate and a bottom alignment plate and the cutting plate is disposedtherebetween. The top and bottom alignment plates can be joined togetherby a plurality of vertical posts that pass through slots in the cuttingplate to maintain the fixed position of the top and bottom platesrelative to each other while permitting movement of cutting plate. Thetop plate, bottom plate and cutting plate can each have a plurality ofholes that are adapted to be concentrically aligned to facilitateblister formation. In certain embodiments, the holes of the top plateare larger than the holes of the bottom plate.

The cutting plate can includes a plurality of holes suitable forconcentric alignment with holes in the alignment plate in a firstposition to facilitate blister formation and a plurality of cuttingsurfaces suitable for cleaving blister in a second position.

The harvester can further include an actuator for moving the cuttingplate from the first position to the second position and the actuatorcan configured to also at least partially retract the cutting platefollowing blister cleavage.

These and other aspects of the devices of the invention are described inthe figures, description and claims that follow. While several improveddesign features have been individually described, such features are notmutually exclusive of each other. Any combination of design featuresdisclosed herein can be used integrated into the devices of theinvention. These design features and other aspects of the devices of theinvention are described in the figures, description and claims thatfollow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 provides a diagram showing the anatomy of skin.

FIG. 2 panels A-C are schematics showing a device for generating andharvesting a plurality of micrografts. Panel A provides an exploded viewof the device. Panel B provides a top view of the assembled device.Panel C provides a side view of the assembled device.

FIG. 3 panels A-B is a drawing showing a device of the invention forraising a suction blister.

FIG. 4 panels A-D show different devices of the invention for raising asuction blister.

FIG. 5 panels A-B show schematics of head of a device according to theinvention. Panel A provides a top view of the head. Panel B shows a sideview of the head.

FIG. 6 provides a diagram showing an external schematic of a device witha head coupled to a hollow body.

FIG. 7A is a schematic depicting the components of an exemplaryembodiment of a blister harvesting device according to the invention;FIG. 7B is a schematic depicting the components of an exemplaryembodiment of a blister generation module for coupling with the blisterharvesting device of FIG. 7A.

FIGS. 8A-8C are schematics depicting the assembly procedure of thecomponents depicted in FIGS. 7A and 7B.

FIG. 9 is a schematic depicting the components of an exemplaryembodiment of a cutter assembly for use in the devices according to theinvention.

FIG. 10A is a schematic depicting an exemplary embodiment of a deviceaccording to the invention in a blister generation mode; FIG. 10B is aschematic depicting an exemplary embodiment of a device according to theinvention in a blister harvesting mode.

FIGS. 11A-11C are schematics depicting the blister generation stepsusing the device mode depicted in FIG. 10A.

FIG. 12A-12C are schematics depicting the blister harvesting steps usingthe device mode depicted in FIG. 10B.

FIG. 13 is exploded schematic perspective view of another embodiment ofa skin harvester according to the invention.

FIG. 13A is a schematic perspective view of the harvester of FIG. 13 asassembled.

FIG. 13B is a schematic perspective sectional view of the harvester ofFIG. 13.

FIG. 13C is an exploded schematic perspective view of the cutter andguide plates of the harvester of FIG. 13.

FIG. 13D is a top view of the cutter and guide plates of the harvesterof FIG. 13.

FIG. 13E is a top view of a plate connector assembly of the harvester ofFIG. 13.

FIG. 14A is a perspective view of the harvester of FIG. 13 in an initialposition to further illustrate the cutting mechanism.

FIG. 14B is sectional side view of the cutter plate drive elements ofthe harvester in an initial position.

FIG. 15A is a perspective view of the harvester of FIG. 13 in a cockedposition (handle up) to further illustrate the cutting mechanism.

FIG. 15B is sectional side view of the cutter plate drive elements ofthe harvester in the cocked position.

FIG. 16A is a perspective view of the harvester of FIG. 13 in a mid-cutposition to further illustrate the cutting mechanism.

FIG. 16B is sectional side view of the cutter plate drive elements ofthe harvester in mid-cut position.

FIG. 17A is a perspective view of the harvester of FIG. 13 intransitional position (from cutting to retraction) to further illustratethe cutting mechanism.

FIG. 17B is sectional side view of the cutter plate drive elements ofthe harvester in the cut-to-retract transitional position.

FIG. 18A is a perspective view of the harvester of FIG. 13 in a final(stroke completion) position to further illustrate the cuttingmechanism.

FIG. 18B is sectional side view of the cutter plate drive elements ofthe harvester in the final (partially retracted) position.

DETAILED DESCRIPTION

The present invention generally relates to a single device that canraise a blister (e.g., a suction blister) and cut the raised blister,i.e., a blister raising device integrated with a cutting member. Suchdevices are useful for harvesting skin grafts.

In certain embodiments, a device as shown in FIG. 2 panels A-C is usedto raise and cut a plurality of skin grafts. Device 200 includes a frame201 and a lid 202. Fitted into the frame is a bottom plate 203, a cuttergrid plate 204, a cutter plate 205, and a top plate 206. The bottomplate 203, the cutter plate 205, and the top plate 206, each include ahole array 211. Once assembled, the hole array 211 of each of plates203, 205, and 206 are aligned. The size of the holes in the hole arraywill depend on the size of the graft needed, with larger holes beingused to produce larger grafts. A first substrate 207 interacts with thetop plate 206 and will receive the harvested grafts.

Device 200 further includes an actuation block 208, actuation bar 209,and actuation block guides 210. Actuation components 208, 209, and 210control movement of the cutter plate 205. The frame 201 includes avacuum stop 212 and the lid 202 includes a suction hole barb 213. Onceassembled, the frame 201 and lid 202 are arranged such that the vacuumstop 212 and the suction hole barb 213 are aligned with each other (FIG.2 panel B). A vacuum source is then connected to the device 200 suchthat negative pressure can be generated within the device. The device200 can be held together by clamp screws 214. Device 200 may alsoinclude a heating element.

To produce and harvest the plurality of skin grafts, device 200 isplaced on a donor site, such as an inner thigh of a patient. The vacuumsource is turned on, producing negative pressure within device 200. Thenegative pressure causes the skin to be pulled toward lid 202, with aplurality of different portions of skin being pulled through each holearray 211 in each of plates 203, 205, and 206. Such action results ingeneration of many microblisters. Once the microblisters are raised,actuation components 208, 209, and 210 are engaged to move cutter plate205. The movement of cutter plate 205 disrupts the alignment of the holearrays 211 in each of plates 203, 205, and 206, and results in cuttingof the microblisters. The cut microblisters are captured on the firstsubstrate 207 that is above top plate 206. In this manner, there isprovided a spaced apart array of micrografts. The amount of negativepressure applied, the amount of time the vacuum is maintained, and/orthe depth of the holes in plate 206 (i.e., the plate thickness)determine what type of graft will be harvested, e.g., epidermal graft,split thickness graft, or full thickness graft. Generally, eachmicrograft will have a lateral dimension of less than about 2 mm e.g.,100 to 2000 microns.

Another aspect of the invention provides a device for obtaining a singleskin graft. Such devices of the invention include a hollow body having adistal end configured for placement on skin, a mechanism for raising ablister, and a cutter integrated in the body for cutting the blisterproduced on the skin.

A gauge for monitoring blister formation can be incorporated within oneor more plates 203, 205, and 206. The gauge is preferably proximal toone or more holes of hole array 211 through which the blisters areformed. For example, the gauge can be located on the plate next to oneor more holes of hole array 211, or on an inner wall of one or moreholes of hole array 211. The gauge can be configured to provide minimumindicator of a sufficient height or dimension for a blister to be cut,and/or a maximum indicator of a sufficient blister dimension to avoidexcessive patient discomfort by application of the device beyond anecessary period of time.

Each hole within the hole array has a depth substantially equal to thethickness of the plate. In certain embodiments, the gauge is acounterbore through one or more of the holes within hole array 211. Thecounter bore serves as a marker to indicate to the user (e.g.,clinician) when the blister has reached a dimension sufficient to becut. The counterbore can be approximately one-half to three-quarters ofthe depth of the hole as measured from the bottom or distal-most surfaceof the plate (i.e., the surface closest to the skin). For example, ifthe plate is 0.3 inches thick, the counter bore is 0.15 inches to 0.225inches, as measured from the bottom or distal-most surface of the plate.

Alternatively, the gauge can be one or more calibration marks locatedproximal to or within one or more holes through which the blisters areraised. For example, the calibration marks can be one or more lineshaving a known length that are drawn, painted or etched onto the surfaceof the plate proximal to one or more of the holes. For example the oneor more lines have a length of about 0.1 mm, about 0.2 mm, about 0.3 mm,about 0.4 mm, about 0.5 mm, about 1.0 mm, about 2.0 mm, about 3.0 mm,about 4.0 mm, about 5.0 mm, about 6.0 mm, about 7.0 mm, about 8.0 mm,about 9.0 mm, about 10.0 mm, about 11.0 mm, about 12.0 mm, about 13.0mm, about 14.0 mm, about 15.0 mm, about 16.0 mm, about 17.0 mm, about18.0 mm, about 19.0 mm, about 20.0 mm, about 21.0 mm, about 22.0 mm,about 23.0 mm, about 24.0 mm, or about 25.0 mm. Alternatively, at leasttwo calibration marks can be drawn, painted or etched onto the surfaceof the plate proximal to one or more of the holes, and the distancebetween the at least two calibration marks can be a known length, forexample about 0.1 mm, about 0.2 mm, about 0.3 mm, about 0.4 mm, about0.5 mm, about 1.0 mm, about 2.0 mm, about 3.0 mm, about 4.0 mm, about5.0 mm, about 6.0 mm, about 7.0 mm, about 8.0 mm, about 9.0 mm, about10.0 mm, about 11.0 mm, about 12.0 mm, about 13.0 mm, about 14.0 mm,about 15.0 mm, about 16.0 mm, about 17.0 mm, about 18.0 mm, about 19.0mm, about 20.0 mm, about 21.0 mm, about 22.0 mm, about 23.0 mm, about24.0 mm, or about 25.0 mm. As the blister is formed, the lateraldimension of the blister can be compared to the one or more calibrationmarks to gauge when the blister is ready to be cut.

In yet another embodiment, the calibration marks may be one or moremarkings that are drawn, painted or etched onto the inner wall of one ormore holes within hole array 211 of the plates. Such markings canindicate a minimum depth within the hole that is sufficient for ablister to be cut, and a maximum level for sufficient blister formationto avoid excessive patient discomfort by application of the devicebeyond a necessary period of time.

In certain embodiments, a device as shown in FIG. 3 panel A is used toobtain a skin graft. Device 400 includes a hollow body 401 and amechanism for raising a blister 402. Hollow body 401 includes a distalend 403 that is configured for placement on the skin. Such a distal endmay include an orifice plate 404. Orifice plate 404 determines the sizeand the shape of the blister or blisters that will be raised. Orificeplate 404 may be any shape or size and will depend on the blister to beraised. Generally, the diameter or lateral dimension of the blister maybe from about 6 mm to about 12 mm, although larger or smaller blistersizes may be used.

The mechanism for raising a blister may be a vacuum component, a heatingcomponent, or a combination thereof. An exemplary heating component is alight source. In a particular embodiment, mechanism 402 is a combinationof a vacuum component and a heating component.

The hollow body 401 further includes a cutter 405, which includes cutterplate 406 and a hole 407 (FIG. 3 panel B). Device 400 further includesan actuation block 408, actuation bar 409, and actuation block guides410. Actuation components 408, 409, and 410 control movement of thecutter 405.

Blister formation is accomplished by attaching the distal end 403 ofhollow body 401 to donor site of a patient, such as an inner thigh of apatient. Hook and loop fastener straps may be used to keep the device inplace. The heating component of blister raising mechanism 402 provides aslight warming of orifice plate 404, which is in direct contact with thepatient's skin surface. The application of a moderate negative pressureto the chamber interior from the vacuum component of blister raisingmechanism 402, results in the patient's skin being gently drawn throughthe opening in orifice plate 404. The result is a blister or blisters,approximately the size of the opening in orifice plate 404. The producedblister may be fluid-filled or may not contain any fluid, i.e., ablister having air within. The skin and blister area is generally notdamaged and patient discomfort is minimal.

The cutter 405 is positioned in hollow body 401 such that upon raisingthe blister, at least a portion of the blister protrudes through hole407 in cutter plate 406. The actuation components 408, 409, and 410 areengaged to move cutter plate 406. The movement of cutter plate 406disrupts the alignment of hole 407 with the other components of device400, and results in cutting of the raised blister.

Preferably, the blister raising mechanism 402 is capable of emittingheat ranging between about 100° C. to about 750° C. (e.g., about 500°C.). In certain aspects, the blister raising mechanism 402 emitselectromagnetic radiation having a wavelength ranging between about 10nm and about 3000 nm. In certain aspects, electromagnetic radiationemitted from blister raising mechanism 402 is reflected off one or moreof the surfaces within the device, back to mechanism 402, causing it tooverheat and burnout. To prevent overheating of mechanism 402, at leastone plate of plates 203, 205, and 206 and/or orifice plate(s) 404 caninclude at least one surface configured for attenuating the reflectionof electromagnetic radiation emitted from mechanism 402. Preferably suchsurface is the surface facing mechanism 402 when the device is fullyassembled.

For example, at least one surface of one or more of plate members 206,205, 203 and/or orifice plate 404 can be coated with a material thatsubstantially attenuates reflection of the electromagnetic radiation(e.g., by absorbing) emitted from mechanism 402. Suitable materialsinclude, for example, a thermoplastic polymer coating. In a particularembodiment, the thermoplastic polymer is a fluoropolymer such aspolytetrafluoroethylene. Preferably, the coating material is a darkcolor such as a substantially black, brown, blue or purple color.

Alternatively, one or more of plate members 206, 205, 203 and/or orificeplate 404 can be anodized, electroplated or painted a dark color such asblack, brown, blue or purple to attenuate the reflection (e.g., absorb)of electromagnetic radiation emitted from mechanism 402.

In yet another embodiment one or more of plate members 206, 205, 203and/or orifice plate 404 can be abraded, scuffed, brushed, or the like,to minimize or remove a glossy or shiny surface appearance in order toattenuate reflection of electromagnetic radiation from mechanism 402.

FIG. 4 panel A shows a device 500 that further includes a chamber 511for capturing the cut blister. Chamber 511 is positioned in hollow body501 and above cutter 505. Chamber 511 may be removable from device 500.Chamber 511 may include multiple configurations. For example, chamber511 may include a retractable bottom. The bottom is in an open positionwhen chamber 511 is inserted into hollow body 501. In the open position,chamber 511 is able to receive the cut blister. Once the cut blister isin chamber 511, the bottom of the chamber is closed, capturing theblister in chamber 511. Chamber 511 may then be removed from device 500.

In another embodiment, chamber 511 includes a substrate 512 (FIG. 4panel C). In this embodiment, device 500 is configured such thatsubstrate 512 is positioned in chamber 511 so that upon raising theblister, a portion of the blister contacts the substrate and becomesattached to the substrate. Cutter 505 then cuts the blister, and the cutblister becomes attached to the substrate 512 in chamber 511. Chamber511 is then removed from device 500, and substrate 512 may be removedfrom chamber 511. In other devices, a vacuum, instead of a substrate, isused to hold the cut blister within the chamber.

In certain embodiments, device 500 does not use a chamber, rather asubstrate 512 is directly integrated with device 500 in order to capturethe cut blister (FIG. 4, panel D). Once captured, substrate 512 havingan attached cut blister may be removed from device 500.

In certain embodiments, the device 500 includes a substrate compressionmechanism for pressing the substrate against the blister to ensure thatthe entire blister surface contacts the substrate 512. Full contactbetween the entire blister surface and the substrate ensures transfer ofthe blister onto the substrate when the blisters are cut. In certainembodiments, the compression member is movably coupled to an exteriorsurface of the hollow body and actuated by an actuation member coupledto the compression member.

The compression member can be a plate having approximately the same sizeand shape as substrate 512. The plate can be coupled to the hollow bodyvia a hinged mechanism or axle member and is actuated by an extensionarm or handle fixedly attached to the plate. The extension arm/handle isengineered to apply at least about 2×, at least about 3×, at least about4×, at least about 5×, at least about 6×, at least about 7×, at leastabout 8×, at least about 9×, at least about 10×, at least about 15×, atleast about 20×, at least about 25×, at least about 30×, at least about35×, at least about 40×, at least about 50×, at least about 75×, atleast about 100× the pressure applied to the extension arm/handle ontothe plate.

Alternatively, the compression mechanism can be a cylindrical rollerdisposed about an actuation arm that defines a longitudinal axis.Movement of the arm in a lateral direction translates into rotationalmovement of the cylinder about the longitudinal axis of the arm, suchthat the cylinder is rolled across the surface of the substrate 512 topress the substrate against the blisters.

The compression member and/or actuation member are preferably reusable.Alternatively, the compression member and/or actuation member are madeof a disposable material. Materials for the construction of thecompression plate or cylinder can be any substantially solid materialsuch as an elemental metal, a metal alloy, a glass, a crystal, or apolymer. In certain embodiments, the compression member and/or actuationmember are made of titanium or stainless steel.

In certain embodiments, the devices according to the invention include ahead portion that can be removably coupled with the hollow body 401 ofthe device. FIG. 5 shows an exemplary embodiment of a removable head 600that includes a blister raising mechanism 402 (e.g., a heating element)for raising a suction blister. The head 600 includes a topmost, proximalportion 610, and a distal portion 620 that couples with the hollow bodyof the device. The head 600 is coupled to the hollow body 401 via holes608. After attachment of head 600 to the hollow body 401, a vacuumsource can be attached to suction tubing 604 to generate negativepressure within the hollow body of the device. FIG. 6 shows head 600coupled to hollow body 401 (collectively 700).

In certain embodiments, the head device includes one or more viewingwindows 602. The viewing windows are located to provide optimal viewingof blister formation within the hollow body of the device. As shown inFIG. 5, a plurality of viewing windows 602 can be integrated within thehead 600 to allow for alternative views of blister formation, or allowmore than one user to monitor the development of the blisters. Incertain embodiments, an ocular shield circumscribes the viewing lenssuch then when the user is viewing blister formation, the shieldattenuates entrance of ambient light into the viewing lens.

The viewing window 602 can be made of any transparent material. Inpreferred embodiments, the viewing window 602 is comprised of opticalquality material, for example an optical polymer, an optical glass, oran optical crystal. Such materials can further include one or more of ananti-fogging material, an anti-scratch coating, or an anti-glarecoating, located on either the or both the interior surface, theexterior surface, or both.

In certain embodiments, the viewing window is made of a heat resistantoptical polymer, optical glass, or optical crystal to prevent warping ordistortion from the heating element of the blister raising mechanism 402within the head 600.

At least a portion of the viewing window 602 can further include amagnification lens to facilitate viewing of the blisters duringformation. The magnification power of the lens can be at least about 2×,at least about 3×, at least about 4×, at least about 5×, at least about6×, at least about 7×, at least about 8×, at least about 9×, at leastabout 10×, at least about 15×, at least about 20×, at least about 25×,at least about 30×, at least about 35×, at least about 40×, at leastabout 50×, at least about 75×, at least about 100×.

In still other embodiments, the viewing window 602 can include one ormore calibration marks etched or painted on the viewing window 602 formonitoring blister formation. Where the viewing window 602 includes amagnification lens, the calibration marks can be calibrated to themagnification power of the lens to approximate the actual dimensions ofthe forming blister, such as the actual height, the actual diameter, orboth. When the desired blister size is formed as gauged by thecalibration marks, the blisters are cut.

As previously described, the head 600 can include a mechanism forraising a blister 402. Such mechanism typically includes a heatingelement, such as nichrome wire, and is located in the topmost, proximalportion 610 of head 600.

In certain embodiments of invention, head 600, includes a transparent ora translucent surface 620 forming the distal side 612 of the head 600(i.e., distal to the heating element). The transparent or translucentsurface is made of a material that facilitates the transmission ofelectromagnetic radiation emitted from the heating element within head600 to one or more plate members incorporated within the hollow body,thereby warming the plate members and subsequently the skin surface.

In certain aspects, the transparent or translucent surface is made ofmaterial that allows light having a wavelength between about 10nanometers to about 3000 nanometers to be transmitted through thesurface. Suitable materials for transmission of light within such rangeincludes, for example, crystalline materials such as sapphire, quartz,silicon, garnet, sillenite, fused silica, fused quartz, titaniumdioxide, zinc selenide, calcium fluoride, barium fluoride, zincsulphide, caesium iodide, germanium, thallium bromo-iodide, lithiumfluoride, magnesium fluoride, potassium bromide, sodium chloride, orstrontium fluoride. The crystalline material can polarized.

Other suitable materials include glass such as silica glass, fluorideglass, aluminosilicate glass, phosphate glass, borate glass,chalcogenide glass, or polymer glass. The glass can be polarized.

In certain aspects, the head 600 includes two transparent or translucentsurfaces 620 forming the distal side 612 of head 600. The two platessurfaces are in a stacked configuration with an airspace in betweenthem. The airspace between the transparent or translucent surfaces isabout 0.1 mm, about 0.2 mm, about 0.3 mm, about 0.4 mm, about 0.5 mm,about 0.6 mm, about 0.7 mm, about 0.8 mm, about 0.9 mm, about 1.0 mm,about 2.0 mm, about 3.0 mm, about 4.0 mm, about 5.0 mm, about 6.0 mm,about 7.0 mm, about 8.0 mm, about 9.0 mm, about 10.0 mm, about 11.0 mm,about 12.0 mm, about 13.0 mm, about 14.0 mm, about 15.0 mm, about 16.0mm, about 17.0 mm, about 18.0 mm, about 19.0 mm, about 20.0 mm, about21.0 mm, about 22.0 mm, about 23.0 mm, about 24.0 mm, or about 25.0 mm.

The two transparent or translucent surfaces can be the same materials,or different materials. For example, the two surfaces can both be madeof a glass or crystalline material. Alternatively, one of the surfacesis a glass material, while the other surface is a crystalline material.

In another aspect, the invention relates to an integrated device forgenerating micrografts and transferring micrografts. More specifically,the invention relates to a device for generating substantially planarmicrografts and for preparing a surgical dressing to facilitatepresentation of the micrografts to a patient in need thereof. The deviceof the invention can be used to prepare any type of skin graft, such asan epidermal skin graft, a split thickness graft, or a full thicknessgraft. However, the device of the invention is particularly well suitedfor preparing skin grafts including only or substantially only theepidermal layer of skin. The device of the invention can be used forautografts, allografts, or xenografts. In preferred embodiments, thegrafts are autografts.

Referring now to FIGS. 7A and 7B, device 1200 includes a top housing1201, a cutter assembly 1202 and a base housing 1203. The top housingincludes a rotatable handle 1213 that is coupled to the cutter assembly1202. The top housing further includes a strap 1211 for coupling thedevice 1200 (once assembled) against a skin surface. The strap may beadjustable in size, or may be a fixed size. The top housing 1201 isconfigured to removably receive a blister generation module 1210 thatincludes a blister generation device 1204 and an adaptor plate 1205(FIG. 2B).

FIGS. 3A-3C depict the assembly of device 1200. As shown in FIG. 3A,cutter assembly 1202 is inserted into top housing 1201. Top housing 1201is then coupled to base housing 1203 via one or more threaded screws1212 that are received by a corresponding threaded holes 1218 in basehousing 1203, such that cutter assembly 1202 is disposed in between tophousing 1201 and bottom housing 1203 (FIG. 3B). As shown in FIG. 3C, theblister generation module 1210 is then inserted into top housing 1201.In certain embodiments, the bottom of adaptor plate 1205 that interfaceswith top housing 1201 includes a gasket around the bottom perimeter ofthe plate 1205 to create an airtight seal between adaptor plate 1205 andtop housing 1201 when coupled together. The blister generation device1204 of the blister generation module 1210 is coupled to an opening 1205a within adaptor plate 1205. In certain embodiments, a gasket isdisposed within opening 1205 a to form an airtight seal between blistergeneration device 1204 and adaptor plate 1205 when coupled together.

Referring now to FIG. 4, the cutter assembly 1202 of device 1200 isshown. The cutter assembly 1202 includes a bottom plate 1202 a, a middleplate 1202 b, and a top plate 1202 c, each of which include an array ofopenings 1214 (e.g., holes or slots) (sometimes referred to herein ashole array 1214). One or more openings of the hole array 1214 in thebottom 1202 a, middle 1202 b and/or top 1202 c plates define a cuttingedge or surface 1215. Preferably one or more openings in the hole array1214 of at least the middle plate 1202 b define a cutting edge orsurface 1215 (FIG. 4). The three plates are assembled in a stackedconfiguration with the middle plate 1202 b being coupled to the bottomplate 1202 a, and the top plate 1202 c being coupled to the middle plate1202 b. One or more of plates 1202 a, 1202 b and 1202 c are configuredto be movable in a lateral direction relative to each other. Forexample, the middle plate 1202 b may be laterally movable relative tothe bottom plate 1202 a, the top plate 1202 c, or both. The top plate1202 c may be movable relative to the middle plate 1202 b, the bottomplate 1202 a, or both. In certain embodiments, the one of more of plates1202 a, 1202 b and 1202 c are configured to laterally move within afixed distance relative to each other.

The middle plate 1202 b and/or top plate 1202 c can be coupled to theirrespective plates in the stacked configuration via at least onefrangible section which serves to keep the plates in alignment until alateral force is applied to the middle 1202 b and/or top 1202 c plate,which breaks the frangible section(s) and allows lateral movement of theplates relative to each other. In a particular embodiment, at least themiddle plate 1202 b is coupled to the bottom plate 1202 a via at leastone frangible section. The at least one frangible section is configuredto break when a lateral force is applied to the middle plate 1202 b,allowing the middle plate 1202 b to move in a lateral direction relativeto the bottom plate 1202 a, the top plate 1202 c, or both. Preferably,middle plate 1202 b is configured to laterally move within a fixeddistance relative to the bottom plate 1202 a and/or top plate 1202 c. Ina particular embodiment, the middle plate 1202 b includes one or moregrooves or channels 1216 that are configured to receive a pin 1217vertically extending from bottom plate 1202 a. Pin 1217 is received atone end of channel 1216 when the frangible section is intact, andlaterally slides within channel 1216 to the opposite end when thefrangible section is broken, such that the lateral movement of plate1202 b relative to plate 1202 a and/or 1202 c is fixed by the movementof pin 1217 within channel 1216.

One or more coupling members can be disposed between the plates to formthe frangible sections, as described in further detail below. The one ormore coupling members are disposed between the openings within holearray 1214. Alternatively, the one or more coupling members are disposedbetween the plates outside of hole array 1214. The frangible coupling ofthe plate members to each other can be accomplished using a mechanicalstamping technique, a mechanical punch technique, spot welding, photoetching, an epoxy, an adhesive, mechanical compression, a snap-fitassembly, a tongue and groove assembly, a post and bar assembly, afrangible pin, or any combination thereof.

In certain embodiments, the middle plate 1202 b and/or top plate 1202 ccan be coupled to their respective plates in the stacked configurationvia at least one elastic member or spring member which serves to keepthe plates in alignment until a lateral force is applied to the middle1202 b and/or top 1202 c plate, which allows the elastic/springsection(s) to flex and allows lateral movement of the plates relative toeach other. Upon removal of the lateral force, the elastic/springsections relax, which allows the plates to return to their originalpositions such that the hole arrays 1214 between the plates are onceagain in concentric alignment. The one or more elastic coupling membersor spring members can be disposed between the openings within hole array1214. Alternatively, the one or more elastic coupling members or springmembers can be disposed between the plates outside of hole array 1214.

Preferably, the hole arrays 1214 of the bottom 1202 a, middle 1202 b andtop 1202 c plates include holes that are substantially similar in sizeand substantially cylindrical in shape. The size of the holes in eachhole array 1214 will depend on the size of the graft needed, with largerholes being used in each plate to produce larger grafts. In certainembodiments, the holes in the hole array 1214 range between 1 mm and 12mm in diameter, or any specific value in between. For example, thediameter of the holes in the hole array 1214 of one or more of plates1202 a, 1202 b and 1202 c can be 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, 3.5mm, 4 mm, 4.5 mm, 5 mm, 5.5 mm, 6 mm, 6.5 mm, 7 mm, 7.5 mm, 8 mm, 8.5mm, 9 mm, 9.5 mm, 10 mm, 10.5 mm, 11 mm, 11.5 mm or 12 mm. In certainembodiments, the holes in hole array 1214 vary in size and/or shapebetween the bottom plate 1202 a, middle plate 1202 b and/or top plate1202 c. Once plates 1202 a, 1202 b and 1202 c of cutter assembly 1202are assembled (i.e., in the stacked configuration), the hole array 1214of each of plates 1202 a, 1202 b, and 1202 c are aligned. In aparticular embodiment, hole arrays 1214 of plates 1202 a, 1202 b, and1202 c are concentrically aligned.

The device 1200 has two modes of operation: 1) a blister generation mode(FIG. 5A); and 2) a blister harvesting mode (FIG. 5B). As shown in FIG.5A, the blister generation mode includes the assembly with the blistergeneration module 1210. The blister generation module 1210 is removedfrom the device assembly for blister harvesting mode (FIG. 5B). Toproduce and harvest a plurality of substantially planar micrografts,device 1200 in the blister generation mode (i.e., with blistergeneration module 1210, as shown in FIG. 5A), is placed on a donor site1220 such as an inner thigh of a patient (FIG. 6A). Strap 1211 is usedto keep the device 1200 in place against the skin surface of donor site1220. The blister generation device 1204 is activated byturning/cranking handle 1204 a of blister generation device 1204. Theblister generation device 1204 utilizes a vacuum component, a heatingcomponent, or a combination thereof, for raising skin blisters. Anexemplary heating component is a light source. In a particularembodiment, mechanism is a combination of a vacuum component and aheating component.

In certain embodiments, the blister generation device 1204 is a suctionblister device for suction blister grafting. Suction blister graftinginvolves raising a skin blister, and then cutting off the raisedblister. An exemplary suction blister grafting technique is shown inAwad, (Dermatol Surg, 34(9):1186-1193, 2008), the content of which isincorporated by reference herein in its entirety. This article alsoshows various devices used to form suction blisters. A suction blisterdevice is also described in Kennedy et al. (U.S. Pat. No. 6,071,247),the content of which is incorporated by reference herein in itsentirety. An exemplary device is the commercially available NegativePressure Cutaneous Suction System from Electronic Diversities(Finksburg, Md.).

A device for raising a suction blister typically operates by use ofsuction chambers that are attached to a patient's skin. An instrumenttypically contains a power source, a vacuum pump, temperature controlsand all related controls to operate multiple suction chambers. Thesuction chambers are connected to the console by a flexible connection.Each of the chambers is controlled by a preset temperature control toprovide an optimal skin warming temperature. Both chambers share anadjustable common vacuum source that affects all chambers equally.

The chamber heating system provides a slight warming of an orifice plateof the device, which is in direct contact with the patient's skinsurface. The negative pressure chamber is fabricated of mostly plasticcomponents, with two removable threaded caps. The upper cap is fittedwith a clear viewing lens so that the actual blister formation can beobserved. The opposite end of the chamber is fitted with a removableorifice plate that is placed on the patient's skin. Since this plate issimply threaded onto the chamber end, multiple plates with differentopening patterns can be interchanged as desired.

The interior of the device is warmed and illuminated by an array of lowvoltage incandescent lamps. This lamp array is controlled from theinstrument console temperature controller, cycling as needed, tomaintain the set point temperature. The heat from these lamps isradiated and conducted to the orifice plate, which then warms thepatient's skin. The chamber is connected to the console via a compositevacuum and low voltage electrical system. Quick connections are used forthe vacuum and electrical system to facilitate removal and storage.

The Negative Pressure Instrument console is a self-contained fan cooledunit which is designed to operate on 120 VAC 60 Hz power. Vacuum issupplied by an industrial quality diaphragm type vacuum pump, capable ofa typical vacuum of 20 in Hg (0-65 kpa) at 0 CFM. An analog controllerthat is preset to 40° C. provides the temperature control for eachsuction chamber. This provides accurate control of the orifice platetemperature. The instrument console has internal adjustments that allowthe user to recalibrate the temperature setting if desired. Othertemperatures can be preset if desired. The front panel includes a vacuumgauge and vacuum bleeder adjustment to regulate the vacuum to bothchambers. The console front panel also contains the connections for thechamber assemblies.

The application of a moderate negative pressure from the blistergeneration device 1204 causes the patients skin to be gently drawnthrough the concentrically aligned hole arrays 1214 of plates 1202 a,1202 b and 1202 c in cutter assembly 1202 (FIG. 6B). Such action resultsin generation of a plurality of raised microblisters 1221, particularlyepidermal microblisters. The blisters 1221 may or may not befluid-filled. The plurality of suction blisters 1221 generated are ofuniform size, approximately the size of the openings/holes in the holearrays 1214 of the three plates of cutter assembly 1202, and areuniformly spaced in accordance with the configuration of the holes inhole array 1214, such that a plurality of substantially planarmicroblisters 1221 are generated. The skin and blister area is generallynot damaged and patient discomfort is minimal.

Once the substantially planar microblisters 1221 are raised/generatedthe device is converted into the blister harvesting mode by removing theblister generation module 1210 from the top housing 1201, therebyexposing the hole array 1214 in the top plate 1202 c of cutter assembly1202. At least a portion of the raised microblisters 1221 protrudethrough the top of the hole array 1214, as shown in FIGS. 6B and 6C. Asubstrate 1219 is applied to the surface of hole array 1214, as shown inFIGS. 5B and 7A, such that the substrate 1219 is in direct contact withthe raised blisters 1221.

To cut the raised blisters 1221, handle 1213 is rotated in a clockwiseor counterclockwise direction (FIG. 7B). Handle 1213 is coupled to themiddle plate 1202 b of cutter assembly 1202 in a configuration thattranslates the rotational movement of the handle 1213 into lateralmovement of middle plate 1202 b. The lateral force applied to middleplate 1202 b by handle 1213 causes middle plate 1202 b to move in alateral direction relative to bottom plate 1202 a and/or top plate 1202c, thereby disrupting the alignment of the hole arrays 1214 betweenplates 2012 a, 2012 b and 1202 c. The lateral displacement of the holearray 1214 of middle plate 1202 b causes the cutting surface 1215defined by one or more holes in the hole array 1214 to cut the raisedblisters 1221. As the raised blisters 1221 are cut, they aresimultaneously transferred/retained on substrate 1219 in the sameconfiguration as generated within hole array 1214, resulting in asubstrate containing a plurality of micrografts that are uniformlyspaced and oriented on the substrate 1219 (i.e., a substrate containinga plurality of substantially planar micrografts).

Certain embodiments of device 1200 integrate consumable/single-usecomponents (e.g., substrate 1219 and/or cutter assembly 1202) andre-usable, sterilizable or cleaned components (e.g., top housing 1201,base housing 1203 and blister generation module 1210), thereby providinga reliable system that is easy to maintain. All components of device1200 that come into contact with the donor and/or recipient tissue (bothsingle-use and reusable components) must be sterile/sterilized to reducethe risk of infection.

In certain embodiments, substrate 1219 includes an adhesive on one sidethat facilitates attachment of the blisters to the substrate. Thesubstrate material may have intrinsic adhesive properties, oralternatively, a side of the substrate may be treated with an adhesivematerial, e.g., an adhesive spray such as LEUKOSPRAY (Beiersdoerf GmbH,Germany). The substrate may be a deformable non-resilient material. Adeformable non-resilient material refers to a material that may bemanipulated, e.g., stretched or expanded, from a first configuration toa second configuration, and once in the second configuration, there isno residual stress on the substrate. Such materials may be stretched toan expanded configuration without returning to their original size. Suchdeformable non-resilient materials tend to be soft, stiff or both softand stiff. Softness is measured on the durometer scale. An example ofsuch a material is a soft polyurethane. A soft polyurethane is producedis as follows. Polyurethanes in general usually have soft and hardsegments. The hard segments are due to the presence of phenyl bridges.In a soft polyurethane, the phenyl bridge is switched out for analiphatic, which is more flexible as its 6 carbon ring has no doublebonds. Therefore, all the segments are soft. On the Durometer Scale, asoft polyethylene is rated about Shore 80A. Other materials suitable foruse with the device 1200 of the invention include low densitypolyethylene, linear low density polyethylene, polyester copolymers,polyamide copolymers, and certain silicones. In a particular embodiment,the substrate 1219 is Tegaderm™.

Ultimately, the substrate containing the plurality of uniformly spacedand oriented (i.e., substantially planar) micrografts is applied to arecipient of site of a patient. Prior to applying the grafts to therecipient site, the site is prepared to receive the grafts using anytechnique known in the art. Necrotic, fibrotic or avascular tissueshould be removed. The technique used to prepare the site will depend ondamage to the recipient site. For example, epidermal tissue, if presentat the recipient site, can be removed to prepare the area for receivingthe micrografts. Burned or ulcerated sites may not need removal ofepidermal tissue, although some cleaning of the site or otherpreparation of the site may be performed. Wounds should be debrided andthen allowed to granulate for several days prior to applying the graft.Most of the granulation tissue should be removed since it has a tendencyto harbor bacteria. Applying silver sulfadiazine to the wound for 10days prior to grafting reduces the bacterial count greatly.

The size of the area at the recipient site can be about the same size asthe area of the substrate having micrografts adhered thereto. This sizegenerally will be greater than the area of the original graft tissuethat was removed from the donor site to form the micrografts. Thedepigmented or damaged skin can be dermabraded with sandpaper or anotherrough material. Alternatively, the epidermal tissue can be removed fromthe recipient site by forming one or more blisters over the area to betreated, e.g., a suction blister or a freezing blister, and the raisedepidermal blister tissue can then be removed by cutting or anotherprocedure.

The substrate having the substantially planar micrografts can be placedover the area to be treated to form a dressing. A portion of thesubstrate having the micrografts can be positioned over the area to berepaired, e.g., the area from which the epidermal tissue has beenabraded or removed for repigmentation. The substrate can be fixed inplace over the treatment area, e.g., using tape or the like. Thesubstrate can be removed after sufficient time has elapsed to allowattachment and growth of the micrografts in the treatment area, e.g.,several days to a few weeks.

Manufacturing Uniform Components for Use in Integrated Devices of theInvention

The invention further relates to methods for manufacturing uniformcomponents for use in the integrated devices of the invention.

In order to generate substantially planar micrografts, the componentswithin cutter assembly 1202 must be substantially uniform with respectto one another. In particular, the planar surfaces of the componentswithin cutter assembly 1202 must be substantially uniform.

In certain aspects one or more coupling members are used to create afrangible coupling between at least two of plate members 1202 a, 1202 band 1202 c. The coupling members are disposed between two or more of theplate members to form a frangible section that is broken upon movementof said plates with respect to each other, as previously described. Thetolerance for any inconsistencies between the planar surfaces of thecoupling members and one or more of the plate members and/orinconsistent dimensions (e.g., width) between the coupling members andone or more of the plate members is very low and could result innon-planar, non-uniform micrografts and device malfunction.

Inconsistencies between the planar surfaces of different stocks of sheetmaterial, manufacturing methods of blanks for the coupling membersand/or plates, and finishing methods of the coupling members and/orplates can each increase tolerance stackups beyond an acceptable level,thereby decreasing the efficiency and function of device and resultingin micrografts that are unusable, and increase patientdiscomfort/distress.

The accumulated variations in production dimensions of the couplingmembers, variations in production dimensions of the plate members, andvariation in the spacing between plate members, can each increasetolerance stackups and decrease device function. In order to optimizethe tolerances within the cutter assembly 1202, the plurality ofcoupling members are preferably formed from the same sheet stock ofmaterial as at least one plate member in the cutter assembly 1202. In aparticular embodiment, the plurality of coupling members and at leastmiddle plate member 1202 b in cutter assembly 1202 are preferably formedfrom the same sheet stock of material (e.g., a single sheet stock ofmaterial). Forming the coupling members and the middle plate member 1202b from the same sheet stock ensures a uniform thickness between thecoupling members and between the coupling members and plate member 1202b, and ensures uniform, planar mating surfaces between the couplingmembers and plate member 1202 b, thereby decreasing tolerance stackupswithin cutter assembly 1202 and ensuring proper device function.

Plate members 1202 a, 1202 b, and 1202 c can be formed from the samematerial, or different materials with respect to each other, so long asthe materials used result in substantially planar mating surfacesbetween the three plates. Preferably, plate members 1202 a, 1202 b, and1202 c are formed from a metallic material (e.g., the same metallicmaterial, or different metallic materials).

In certain embodiments, each of plate member 1202 a, 1202 b, and 1202 cis formed from the same sheet stock of material, preferably a singlesheet stock of material. One or more openings (e.g., holes or slots) areformed within each plate member to form hole arrays 1214 that align whenthe plate members are assembled, as previously described. In certainembodiments, the coupling members are formed from the same sheet stockfrom which the plurality of plate members are generated. Forming thecoupling members and plate members from the same sheet stock ensuresuniformity in the thickness among and between the coupling members andplate members, and uniformly planar mating surfaces between the couplingmembers and plate members, thereby decreasing tolerance stackups withincutter assembly 1202 and ensuring proper device function.

The coupling members can be any shape or dimension sufficient to couplethe plates together without obstructing the holes in the hole arrays1214 through which the suction blisters are raised. For example, thecoupling members can be substantially square or rectangular in shape.Alternatively, the coupling members are substantially circular in shape.In certain embodiments, the coupling members are of a sufficient shapeand size for location between the holes of the hole arrays 1214 of theplate members. In other embodiments, the coupling members are of asufficient shape and size for location along the edges of the pluralityof plates.

Any method can be used to manufacture the plates and/or couplingmembers, such as drilling, milling, laser etching, lithographicprocessing, photo etching, laser ablation and the like. In a particularembodiment, a photo etching process is used to manufacture the platesand/or coupling members.

The frangible coupling between the coupling members and plate memberscan be accomplished using a variety of techniques. For example, thecoupling members can be frangibly coupled between the plate members viaspot welding techniques (e.g., laser spot welding), via an adhesive suchas epoxy, polyurethane, acrylic or a resin, via a frangible pin, asnap-fit or tongue and groove assembly. Such frangible couplingtechniques can be accomplished using one or more manufacturing processessuch as cold-heading, multiple-die forming, multiple-die progression,multiple-die headers, casting, stamping, punching, atomic hydrogenwelding, bare metal arc welding, carbon arc welding, flux cored arcwelding, gas metal arc welding, gas tungsten arc welding, plasma arcwelding, shielded metal arc welding, submerged arc welding, airacetylene welding, oxyacetylene welding, oxygen/propane welding, oxyhydrogen welding, pressure gas welding, resistance spot welding,resistance seam welding, projection welding, flash welding, upsetwelding, co-extrusion welding, cold pressure welding, diffusion welding,explosion welding, electromagnetic pulse welding, forge welding,friction welding, friction stir welding, hot pressure welding, hotisostatic pressure welding, roll welding, ultrasonic welding, electronbeam welding, electroslag welding, flow welding, induction welding,laser beam welding, percussion welding, thermite welding, electrogaswelding, and stud arc welding.

Optionally, a portion of the plate material at or around the site of thefrangible coupling is removed to accommodate at least a portion of thecoupling member by forming a depression at or around the frangiblesection. For example, in one embodiment, laser etching or photo etchingon the plate member is used to circumscribe the coupling point at orproximal to the frangible coupling. In another embodiment, a depressionat or proximal to the plate member can be removed with any method knownin the art, for example drilling, milling, laser etching, photo etching,laser ablation and the like.

FIG. 13 is exploded view of another embodiment of a skin harvesteraccording to the invention. Harvester 2000 includes a bottom element2002 with a strap coupler 2004 (e.g., for joining a hook andfastener-type strap to the harvester to facilitate attachment of theharvester 2000 to a patient's skin, e.g., by wrapping the device arounda patient's leg for harvesting skin from the inner thigh).

The harvester 2000 also includes a cutter assembly with a bottom plate2006, a top plate 2008 and a middle (cutter) plate 2010 configurable toinitially provide concentrically aligned holes through which blisterscan be raised. (The operation of the plates, 2006, 2008 and 2010 of thecutter assembly is similar to that of elements 1202 a, 1202 b and 1202 cdescribed above in connection with FIGS. 7-12.) The harvester 2000further includes a cutter drive sled 2012, handle actuator 2014 and atop element 2016.

FIG. 13A is a schematic perspective view of the harvester 2000 asassembled (with top element 2016 omitted for clarity). FIG. 13B is aschematic perspective sectional view of the harvester 2000.

FIG. 13C is an exploded schematic perspective view of the guide andcutter plates 2006, 2008 and 2010 of the harvester 2000. As describedabove in FIGS. 7-12, the cutter plate 2010 is designed to move adirection parallel to guide plates 2006 and 2008 in a one-time, back andforth motion. Following the formation of microblisters that protrudethrough the aligned holes, the cutter plate moves in the direction 2026to slice the blisters and then moved in the opposite direction 2028 toat least partially retract the blade elements. The alignment of theplates is further illustrated in FIG. 13D, which is a top view of thecutter and guide plates in a configuration where the top holes 2032,bottom holes 2030 and cutter plate holes 2036 are aligned to permitblisters to form and pass through all three plates (The holes of the topplate can be larger than those of the bottom plate to facilitate blisterformation and/or growth of the blister.) The cutter plate holes,however, also provide a cutting edge 2034 (shown in phantom) to occludethe passageway and cleave the blister when the plate 2010 is movedrelative to the top and bottom guide plates 2006, 2008. FIG. 13 Dfurther illustrate one of a plurality of plate connecting posts 2040that join the top and bottom plates together and an alignment slot 2041which allows the cutter plate to move relative to the stationary top andbottom plates 2006, 2008.

The various features of the cutting plate can be formed, for example,lithographically by depositing a resist and patterning it (e.g., byexpose to light) such that portions of an initial plate blank areprotected from etching while other portion can be removed by etching(e.g., to form the holes and alignment slots). The resist can also bepatterned to provide a limited amount of protection to the cutting edgeportions, thereby shaping them to have less thickness (e.g., like aknife edge). The sharpness of the cutting edges can be further enhancedby electro-polishing which will reduce the overall thickness of thecutting plate.

FIG. 13E (taken in conjunction with FIGS. 13C and 13D) illustrate oneway to provide a plate connector assembly. The vertical posts 2040 canbe formed by spot welding the top, bottom and cutter plates together.However, the portion of the cutter plate (“puck” 2046) that joins thetop and bottom plates in the weld is designed to break away from thecutter plate 2010, e.g., at the initiation of the cutting stroke.

The actuator for moving the cutter plate will now be described inconnection with FIGS. 14-18. FIG. 14A is a perspective view of theharvester of FIG. 13 in an initial position with the handle (actuator)2014 in an initial position. The cutter plate 2010 is joined to a sled2012 as discussed above. The handle is linked to the sled 2012 via agenerally cylindrical bar (axle) 2020. As shown in FIG. 14B thecylindrical bar 2020 rotates about an axis when the handle is lifted upor closed. Cylindrical bar 2020, however also has two non-symmetricfeatures: protrusions 2070 and 2074. The handle 2014 thus serves as alever arm.

FIG. 15A is a perspective view of the harvester in a cocked position(handle up) to further illustrate the cutting mechanism. As shown inFIG. 15B this results in protrusion 2070 (e.g., a longitudinal ridge onthe cylindrical axle) engaging with a mating feature 2072 (e.g., agroove in the sled). As the handle is brought down the sled is thusforces to move by the rotation of axle 2020. FIGS. 16A and 16Billustrates the handle in a in a mid-cut position

FIG. 17A is a perspective view of the harvester of FIG. 13 intransitional position (from cutting to retraction) to further illustratethe cutting mechanism. At this point in the rotation of the axle 2020,protrusion 2070 has detached from mating feature 2072 and the secondprotrusion 2074 has engaged with a different portion 2076 (e.g., ashoulder pad) of the sled. As the handle continues its downward portion,the rotation of axle causes the sled to move in the opposition directand, thus retract the cutter plate. FIGS. 18A and 18B illustrate theharvester in a final (stroke completion) position.

In certain embodiments, devices of the invention are configured toproduce epidermal grafts. The skin consists of 2 layers. The outerlayer, or epidermis, is derived from ectoderm, and the thicker innerlayer, or dermis, is derived from mesoderm. The epidermis constitutesabout 5% of the skin, and the remaining 95% is dermis. FIG. 1 provides adiagram showing the anatomy of skin. The skin varies in thicknessdepending on anatomic location, gender, and age of the individual. Theepidermis, the more external of the two layers, is a stratified squamousepithelium consisting primarily of melanocytes and keratinocytes inprogressive stages of differentiation from deeper to more superficiallayers. The epidermis has no blood vessels; thus, it must receivenutrients by diffusion from the underlying dermis through the basementmembrane, which separates the 2 layers.

The dermis is a more complex structure. It is composed of 2 layers, themore superficial papillary dermis and the deeper reticular dermis. Thepapillary dermis is thinner, including loose connective tissue thatcontains capillaries, elastic fibers, reticular fibers, and somecollagen. The reticular dermis includes a thicker layer of denseconnective tissue containing larger blood vessels, closely interlacedelastic fibers, and coarse, branching collagen fibers arranged in layersparallel to the surface. The reticular layer also contains fibroblasts,mast cells, nerve endings, lymphatics, and some epidermal appendages.Surrounding the components of the dermis is the gel-like groundsubstance composed of mucopolysaccharides (primarily hyaluronic acid),chondroitin sulfates, and glycoproteins.

In a graft, the characteristics of the donor site are more likely to bemaintained after grafting to a recipient site as a function of thethickness of the dermal component of the graft. However, thicker graftsrequire more favorable conditions for survival due to the requirementfor increased revascularization. It has been discovered, however, that asubstantially epidermal graft according to the invention is more likelyto adapt to the characteristics of the recipient site.

An epidermal graft refers to a graft that consists of substantiallyepidermal skin and does not include any substantial portion of thedermal layer. A split thickness graft refers to a graft that includessheets of superficial (epithelial) and some deep layers (dermal) ofskin. A full-thickness graft refers to a graft that includes all of thelayers of the skin including blood vessels.

Devices of the invention may be used to harvest a skin graft(s) forrepair of numerous different types of skin damage. For example,harvested grafts may be used to treat burns (e.g., both thermal andchemical burns), blistering, dermatological conditions (e.g.,epidermolysis bullosa or pyoderma gangrenosum), radiation therapyulcers, diabetic ulcers, ischemic ulcers, trophic ulcers, trauma, ordepigmentation (e.g., vitiligo).

In particular embodiments, the skin graft(s) are used to treat vitiligo.Vitiligo is a chronic disorder that causes depigmentation of patches ofskin. It occurs when melanocytes, the cells responsible for skinpigmentation, die or are unable to function. Although patches areinitially small, they often enlarge and change shape. When skin lesionsoccur, they are most prominent on the face, hands and wrists. Somelesions have hyper-pigmentation around the edges. Depigmentation isparticularly noticeable around body orifices, such as the mouth, eyes,nostrils, genitalia and umbilicus.

Vitiligo is generally classified into two categories, non-segmentalvitiligo and Segmental vitiligo. In non-segmental vitiligo (NSV), thereis usually some form of symmetry in the location of the patches ofdepigmentation. New patches also appear over time and can be generalizedover large portions of the body or localized to a particular area.Vitiligo where little pigmented skin remains is referred to as vitiligouniversalis. Non-segmental vitiligo can come about at any age, unlikesegmental vitiligo which is far more prevalent in teenage years.

Segmental vitiligo (SV) differs in appearance, aetiology and prevalencefrom associated illnesses. Its treatment is different from that ofnon-segmental vitiligo. It tends to affect areas of skin that areassociated with dorsal roots from the spine. It spreads much morerapidly than non-segmental vitiligo and, without treatment, it is muchmore stable/static in course and not associated with auto-immunediseases.

To treat vitiligo, an autograft is provided to the site of depigmentedskin. The graft includes melanocytes, and thus upon the recipient siteaccepting the graft, the graft will produce pigmented skin at therecipient site. A donor site of pigmented skin is aseptically cleanedprior to harvesting of a skin graft. Standard methods are used to cleanthe donor site. A typical donor site is an inner thigh, but any area ofpigmented skin may be used.

After cleaning, a skin grafted is harvested using devices of theinvention. Devices described herein raise and cut a blister(s), such asa suction blister. The area of depigmented skin (i.e., the recipientsite), is prepared through aseptic cleaning and dermabrasion. Thegraft(s) is applied to the dermabraded recipient site. The donor siteand the recipient site are dressed and wound care is provided.

INCORPORATION BY REFERENCE

References and citations to other documents, such as patents, patentapplications, patent publications, journals, books, papers, webcontents, have been made throughout this disclosure. All such documentsare hereby incorporated herein by reference in their entirety for allpurposes.

EQUIVALENTS

The invention may be embodied in other specific forms without departingfrom the spirit or essential characteristics thereof. The foregoingembodiments are therefore to be considered in all respects illustrativerather than limiting on the invention described herein. Scope of theinvention is thus indicated by the appended claims rather than by theforegoing description, and all changes which come within the meaning andrange of equivalency of the claims are therefore intended to be embracedtherein.

What is claimed is:
 1. A device for obtaining a skin graft, the devicecomprising: a harvester configured for placement on a target region of apatient's skin and further adapted to form a sealing engagement with ahead that provides negative pressure to the target region such that thetarget region of skin is embraced within an evacuated chamber, theharvester further comprising: at least one alignment plate having aplurality of holes through which skin blisters can be raised in thepresence of negative pressure; and a cutting plate having at least onecutting surface for cleaving skin blisters after they are formed withinthe chamber.
 2. The device according to claim 1, wherein said at leastone alignment plate comprises a top alignment plate and a bottomalignment plate and wherein the cutting plate is disposed therebetween.3. The device according to claim 2, wherein the top and bottom alignmentplates are joined together by a plurality of vertical posts that passthrough slots in the cutting plate to maintain the fixed position of thetop and bottom plates relative to each other while permitting movementof cutting plate.
 4. The device according to claim 2, wherein the topplate comprises a radiation absorbing material.
 5. The device accordingto claim 2, wherein the top plate comprises at least one fluoropolymersurface.
 6. The device according to claim 2, wherein the top plate,bottom plate and cutting plate each have a plurality of holes that areadapted to be concentrically aligned to facilitate blister formation. 7.The device according to claim 6, wherein the holes of the top plate arelarger than the holes of the bottom plate.
 8. The device according toclaim 1, wherein the cutting plate includes a plurality of holessuitable for concentric alignment with holes in the alignment plate in afirst position to facilitate blister formation and a plurality ofcutting surfaces suitable for cleaving blister in a second position. 9.The device according to claim 8, wherein the device further comprises anactuator for moving the cutting plate from the first position to thesecond position.
 10. The device according to claim 9, wherein theactuator is configured to also at least partially retract the cuttingplate following blister cleavage.
 11. The device according to claim 9,wherein the actuator is configured to move the cutting plate from thesecond position to the first position following blister cleavage. 12.The device according to claim 9, wherein the cutting plate and thealignment plate are coupled in the first position to prevent relativemovement thereof, and wherein actuation of the actuator is configured todecouple the cutting plate and the alignment plate.
 13. The deviceaccording to claim 12, wherein the cutting plate and the alignment plateare frangibly coupled via one or more spot welds that are configured tobreak upon actuation of the actuator.
 14. The device according to claim9, wherein rotation of the actuator moves the cutting plate laterallyfrom the first position to the second position.
 15. The device accordingto claim 14, further comprising a sled coupled to the cutting plate, andwherein the actuator comprises a handle and an axle, the axle having afirst protrusion extending therefrom for engaging a first mating featureon the sled so as to move the cutting plate from the first position tothe second position during a first portion of the rotation of theactuator.
 16. The device according to claim 15, wherein a secondprotrusion extending from the axle engages a second mating feature onthe sled so as to move the cutting plate from the second position to thefirst position during a second portion of the rotation of the actuator.17. The device according to claim 14, wherein a single stroke of theactuator moves the cutting plate from the first position to the secondposition so as to cleave the skin blister and from the second positionto the first position to at least partially retract the cutting plate.18. The device according to claim 8, wherein each of the cuttingsurfaces is associated with one of the holes of the cutting plate. 19.The device according to claim 1, wherein the head further comprises asealing surface to engage with a mating surface on the harvester suchthat, when the head is engaged with the harvester on a patient's skin,the evacuated chamber is formed over the target region of skin.
 20. Thedevice according to claim 1, wherein the head further comprising atleast one temperature measuring element for measuring the temperature ofthe skin or evacuated chamber.